Download Diagnostic Testing

Diagnostic Testing
• Laboratory findings
• ↓ insulin-like-growth hormone factor or IGF-1
• ↓ insulin-like-binding protein or IGFBP-3
• Gold Standard Test
• Growth hormone provocative
stimulation test.
• Agents used
• Delayed bone age
• Arginine
• Growth hormone level are not reliable
• Clonidine
• Insulin
• Glucagon
Growth hormone deficiency
• Imagining
• Brain MRI to rule out
pituitary/brain neoplasm
• Treatment
• Recombinant growth hormone shots
at night time
Diabetes Insipidus (DI)
• Central DI:
• Caused by complete or partial deficiency of antidiuretic hormone (ADH) from the
posterior pituitary gland.
• Caused by damage to the hypothalamus or pituitary stalk due hemorrhage,
infarction, surgical or accidental trauma, infection or granulomas.
• Nephrogenic DI:
• Defect in the kidney tubules that interferes with water absorption.
• Medications: lithium, cisplatin, aminoglycosides, rifampin, vincristine, foscarnet
Clinical Presentation
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Intense thirst (polydipsia). Patient may drink from 2-20 liters of water/day
Ice water craving
Polyuria
Hypernatremia:
• Weakness
• Altered mental status
• Seizures
• Coma
Diagnostic Criteria
• Low urine osmolality <300
mOsm/kg
• Elevated plasma osmolality >300
mOsm/kg
• Urine specific gravity <1.001 to
1.010
• Plasma sodium may be elevated or
normal
Treatment of DI
• Central DI
• Oral DDAVP (Desmopressin) 0.05 mg – 0.4 mg twice daily
• Nasal DDAVP 0.05 - 0.1 every 12 hours
• SC, IM or IV DDAVP 1- 4 mcg every 12-24 hours
Prolactinomas
• Prolactin-secreting tumors
• Account for 40% of pituitary tumors
• Is the most frequent pituitary tumor occurring in multiple endocrine
neoplasia syndrome (MEN 1)
Clinical Presentation
Men
Women
• Galactorrhea: most common in
• Galactorrhea: less common in
• Amenorrhea
• Oligomenorrhea
• Infertility
• Decreased libido
• Infertility
• Gynecomastia
females
• Prolactin inhibits LH, FSH and
decreases production of estrogen
males
• Prolactin inhibits: LH, FSH
and decreases production of
Testosterone
Diagnostic Criteria
• Elevated Prolactin level:
• <100 ng/mL: possible prolactinoma
• 100-200 ng/mL: likely prolactinoma
• >200 ng/mL diagnostic of prolactinoma
• Brain MRI to define tumor size and location
Treatment
Pharmacological: First line of Treatment
Dopamine agonists:
Bromocriptine 2.5 to 20 mg/day
Carbegoline 0.25-1.0 mg twice/wk
Surgery:
• Trans-sphenoidal
• Craniotomy (not
preferred)
Type 1 Diabetes
• Autoimmune disorder leading to
destruction of the beta cells of the
pancreas leading to lack of insulin
production.
• Genetics play a role in Type 1 DM
Antibodies to the Pancreas
Glutamic acid decarboxylase (GAD-65) : sensitivity 70-90% specificity 99%
Islet cell antibody (ICA-512): sensitivity 50-70% specificity 99%
Insulin antibodies (IAA):
sensitivity 40-70% specificity 99%
Zinc Transporter 8 (ZnT8): sensitivity 50-70% specificity 99%
Symptoms of diabetes
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Increased thirst (polydipsia)
Frequent urination (polyuria)
Extreme hunger
Weight loss
Fatigue
Blurred vision
Vulvovaginitis or pruritus
Diagnosis of Diabetes
• Two fasting plasma glucose 126 mg/dL or greater
• Oral glucose tolerance test (OGTT):
• 2 hour plasma glucose 200 mg/dL or greater
• Plasma glucose 200 mg/dL or greater with symptoms
• New onset diabetic ketoacidosis
• A1C 6.5% or greater
Treatment of Type 1 & 2 Diabetes
Long Acting Insulin (or Basal Insulin)
Glargine (Lantus)
Onset: 0.8-4 hours
Peak: minimal
Duration: 24 hours
Once daily or twice daily
Detemir (Levemir)
Onset: 0.8-4 hours
Peak: minimal
Duration: 18-20 hours
Once or twice daily
Long Acting Concentrated Insulin
Toujeo (Glargine U300)
Duration of action: >30 hours
Half life: 18-19 hours
Steady state: 5 days
Once daily
Degludec (Tresiba) (U100&U200)
Duration of action: 42 hours
Half life: 25 hours
Steady state: 2-3 days
Use once daily
Rapid Acting Insulin Analogs
Aspart (Novolog)
Onset: 10-20 minutes
Peak: 40-50 minutes
Duration: 3 to 5 hours
Rapid Acting Insulin Analogs
Lispro (Humalog)
Onset: 10-20 minutes
Peak: 40-50 minutes
Duration: 3 to 5 hours
Rapid Acting Insulin Analog
Glulisine (Apidra)
Onset: 10-20 minutes
Peak: 40-50 minutes
Duration: 3 to 5 hours
Management of Diabetes
• Intense Insulin Treatment: Multiple daily injections
Basal insulin (long acting) 50%
Bolus insulin (rapid acting) 50%
• Continuous infusion: Insulin Pumps
Rapid acting insulin
How to calculate Total Daily Dose (TDD) of Insulin
in Adults
All persons ≥ 18 years:
TDD = Weight X 0.5 units/kg/day
e.g: a 25 year old male with weight 72 kg
50% of TDD will be Basal Insulin
Lantus (Glargine) or Levemir (Detemir):
18 units/day
50% of TDD will be Bolus Insulin:
18 units ÷ 3 equal doses
70 kg X 0.5 = 36 units daily
Novolog (Aspart) 6 units @ breakfast
Novolog (Aspart) 6 units @ lunch
Novolog (Aspart) 6 units @ dinner
Diabetic Ketoacidosis (DKA)
• Is a life threatening condition that is not sustainable without insulin
• The body begins to breakdown fatty tissue and protein
• Build up of acids called “ketones” in the blood and urine which are toxic to
the body.
Electrolytes Imbalance
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High glucose
Low sodium
Potasium is high, normal and then low
Low phosphate
When to Suspect DKA
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Decreased alertness
Rapid “Kussmaul” breathing
Flushed face
Dry skin and mouth
Fruity smell breath (ketones)
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Stomach pain
Nausea and vomiting
Altered mental status
Coma
Criteria for DKA
• Blood glucose >200
• Ketonemia
• Metabolic acidosis:
• ph <7.25
• Serum bicarbonate <15 mmol/L
• Increased anion gap >10
Treatment
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Careful replacement of fluid deficits to correct the dehydration.
Correction of acidosis and hyperglycemia via insulin drip (0.1 units/kg/hr)
Correction of electrolytes imbalance
Treatment of underlying cause: infection
Complications
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Cerebral Edema
Intracranial thrombosis or infarction
Acute tubular necrosis
Peripheral edema
Complications of Diabetes
Diabetic Cataracts:
60% of diabetics will experience
cataracts (cloudiness of the lens).
Correlates with the duration of the
disease and severity of the
hyperglycemia.
Diabetic Retinopathy
After 10-15 years: 25-50%
-After 15 years: 75-95%
-After 30 years: 100%
Glaucoma
--Increased intraocular pressure due
to fluid collection.
--Can lead to blindness due to
damage to the optic nerve.
--Occurs ins 6% of patients with
diabetes.
Diabetic Nephropathy
Labs to order:
• Type 1 DM have 30-40 risk of having
nephropathy after 20 years of
diagnosis.
• Type 2 diabetics have 15-20% risk
• Manifestation: Proteinuria
Morning Microalbumin/creatinine ratio:
<30 mcg/mg is normal
30-300 mcg/mg abnormal
24 hour urine microalbumin (normal <30 mcg/mg)
Treatment:
• Ace-Inhibitor: Zestril (Lisinopril) 10 mg daily
• Angiotensin Receptor blocker: Cozaar (Losartan)25 mg daily
Foot Ulcers
Repetitive stress and high foot
pressure lead to calluses and
ulcerations
Peripheral Neuropathy
-Involvement of only one or
several nerves.
-Characterized by sudden onset
of loss of sensory with
subsequent recovery of all or
most of the function.
Painful Diabetic Neuropathy:
-Hypersensitivity to light touch
-Burning pain at night
Treatment:
-Gabapentin (Neurontin) 900 mg/day
-Amitriptyline (Elavil) 25-75 mg daily
Cardiovascular Complications
Heart Disease:
Microangiopathy leading to congestive
heart failure in diabetics
Coronary atherosclerosis
Myocardial infarction is 3-5 times more
common in diabetics
Hypertension
Hyperlipidemia
Labs: Fasting lipid profile yearly
Treatment: Statins (HMG-coA inhibitors)
Simvastatin (Zocor)
Atorvastatin (Lipitor)
Rosuvastatin (Crestor)
Aspirin 81-321 mg daily
Peripheral Vascular Disease
-Atherosclerosis is markedly accelerated in
the larger arteries.
-Ischemia of the lower extremities is
common
-Erectile dysfunction
-Intestinal angina
Gangrene of the Feet: toes
and leg amputations
Skin complications
Candida Infections:
-erythema and edema below
the breasts, axilla and
between fingers.
-Chronic pyogenic
infections of the skin
-Vulvovaginitis
Treatment:
Antifungal creams
Miconazole (Monistat)
Clotrimazole (Lotrimin)
Fluconazole (Diflucan)150 mg x1
Necrobiosis Lipoidica Diabeticorum
-Degeneration of collagen,
inflammation of the tissues and
blood vessels, capillary
membrane.
-Oval or irregularly shaped
plaques with demarcated
borders located mainly in the
anterior surfaces of the legs.
-Most common in women than
men
Type 2 Diabetes
• Multifactorial: Genetics and
Environmental factors
• Family history of T2DM
• Genes predisposition
• Sex, age, ethnicity
• Excessive caloric intake
• Lack of daily exercise
Pathophysiology
• Insulin resistance
• Inability cells to
respond to stimulation
of insulin
• Precedes the onset of
T2DM
Clinical Presentation: T2DM
Asymptomatic or mild
hyperglycemia:
--glucose 120-140 mg/dL.
Elevated blood sugars: >200 mg/dL
• Polyuria
• Polydipsia
• Blurred vision
• Sexual dysfunction
• Diabetic ketoacidosis (not as common as
Type 1 DM)
Metabolic Syndrome
Men
Women
• Waist circumference >40” (102 cm)
• Waist circumference >35” (88 cm)
• Triglycerides ≥ 150 mg/dL
• Triglycerides ≥150 mg/dL
• High-density lipoprotein (HDL) <40
• High-density lipoprotein (HDL) <50
mg/dL
mg/dL
• Blood pressure≥130/85 mm Hg
• Blood pressure ≥ 130/85 mm HG
• Fasting glucose ≥100 mg/dL
• Fasting glucose ≥ 100 mg/dL
Treatment of T2DM
• Lifestyle modification: first line of treatment
• Healthy eating
• Physical activity
• Weight loss reduces insulin resistance
• Weight loss is recommended for all overweight and obese individuals at risk
for diabetes
Medications for Type 2 DM
• Biguanides: Target organs: Liver and Skeletal Muscles
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Mechanism of action:
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Reduces hepatic glucose output
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Reduces intestinal absorption of glucose
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Improves insulin sensitivity by increasing peripheral glucose uptake and
utilization
Metformin (Glucophage)
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500-1000 mg twice daily
Benefits:
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Low risk for hypoglycemia
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Decreases cardiovascular disease
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Low cost (very inexpensive)
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Disadvantage: Nausea, diarrhea, abdominal cramping, risk for lactic acidosis
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Contraindications: Creatinine >1.4, Liver or heart failure, Age >80 years
Sulfonylureas
• Sulfonylureas (2nd generation)
• Target organ: Pancreas
• Mechanism of action:
• Increase insulin secretion via ß cell
• Glyburide (DiaBeta) 2.5 -20 mg/d
• Glipizide(Glucotrol) 2.5-20 mg/d
• Glimepiride (Amaryl) 2-8 mg/d
Benefits:
• Well tolerated
• Inexpensive
Disadvantage:
• Hypoglycemia
• Weight gain
Dipeptidyl Peptidase IV Inhibitor (DPP-4 inhibitor)
DPP-4 Inhibitors:
Target Organs:
Liver, pancreas (ß cell), Adipose tissue, GI
Mechanism of action:
Increases endogenous glucacon-likepeptide 1)(GLP-1) by inhibiting dipeptidyl
peptidase 4 (DPP-4) that breaks down
gastric inhibitory polypeptide (GIP) and
GLP-1
DPP-4 Inhibitors
Sitaliptin (Januvia)
-100 mg daily
-50 mg in stage 3 renal disease
-25 mg in stage 4 renal disease
Benefits:
-No weight gain
-Well tolerated
-Low risk for hypoglycemia
Saxagliptin (Onglyza)
-5 mg daiy
-2.5 mg in stage 3,4,5, renal disease (CKD)
Linagliptin (Tradjenta)
-5 mg daily
-No adjustment in CKD
Disadvantage:
-Dose adjustment in CKD
-Risk of interfering with the
immune system
Glucagon-Like-Peptide-1 Mimetics (GLP-1)
Target Organ:
Liver, Pancreas (ß cell), Adipose tissue and GI
Mechanism of action:
-↑insulin secretion
-↓glucagon secretion
-slow gastric emptying
-decreases appetite
Exenatide (Byetta, Bydureon)
5-10 mcg twice daily via injection
2 mg once/wk via injection
Liraglutide (Victoza)
0.6-3 mg daily via injection
Albiglutide (Tanzeum)
30-50 mg once a week via injection
Dulaglutide (Trulicity)
0.75- 1.5 mg once a week via injection
Bariatric Surgery
-Leads to near or complete
normalization of glycemia in 50 to
90% of T2DM
-Patients with multiple co-morbidities
and BMI≥ 35 are candidates for
bariatric surgery
Complications of T2DM
Nonketotic Hyperglycemia Hyperosmolar Coma:
Is a form of hyperglycemic coma characterized by:
-Severe hyperglycemia
-Hyper osmolality
-Dehydration
-Absence of ketosis
It tends to occur in patients:
- with mild or occult diabetes
-middle aged or elderly
Nonketotic Hyperglycemia Hyperosmolar Coma
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-weakness & lethargy
Labs
• Glucose >600 - 2400 mg/dL
-polyuria
• Serum Osmolality >310 – 440
Signs and Symptoms
-polydipsia
-profound dehydration
-absence of Kussmaul respirations
-confusion
-coma
mOsm/kg
• No acidosis: pH >7.3
• Serum Bicarbonate >15 mEq/L
• Normal anion gap <14 mEq/L
Lactic Acidosis
Pathogenesis:
-Diabetic patients presenting with profound
acidosis and increased anion gap greater than
15 mEq/L in the absence of ketoacidosis.
-Lactate >5 mmol/L (normal 0.5-2.2 mmol/L)
The Cori Cycle
Causes of Lactic acidosis
Clinical conditions
Tissue hypoxia
hepatic failure
circulatory collapse
Medications
Metformin (Glucophage): high dose
or overdose
Treatment of Lactic Acidosis
-ABC: airway, breathing and circulation
-Correct the offending cause
-Cultures of blood if sepsis is suspected and start antibiotics immediately
-Alkalinization with intravenous sodium bicarbonate to keep pH >7.2 (there is
no evidence that mortality rate is decreased). The use of sodium bicarbonate
remains controversial.
Diabetes and Hypertension
- Most people with diabetes develop high blood pressure during their life.
- Diabetes causes damage to the arteries and makes them targets for atherosclerosis.
- Atherosclerosis leads to high blood pressure, which if not treated, can lead to blood vessel
damage, stroke, heart failure, heart attack, or kidney failure.
- Treatment: Angiotensin-Converting-Enzyme Inhibitor (ACE inhibitor)
Lisinopril (Zestril) 10-40 mg daily
Diabetes and Dyslipidemia
All patient with diabetes must have a fasting lipid profile checked yearly.
Lipid targets:
LDL <100 mg/dL
HDL >40 mg/dL in men; >50 mg/dL in women
Triglycerides: <150 mg/dL
Treatment: HMG-CoA Reductase Inhibitors (Statins)
Simvastatin (Zocor) 10-40 mg/d
Atorvastatin (Lipitor) 10-40 mg/d
Rosuvastatin (Crestor) 10-40 mg/d
Lipid Disorders
Atherosclerosis
• Genetics and environmental factors play a role in the development of
dyslipidemia.
• In the Western society, dyslipidemia affects 90% of the population due to
high fat diet.
• Less than 10% of the cases are related to genetics.
Risk factors for Atherosclerosis
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Hyperlipidemia
Hypertension
Smoking
Diabetes
Physical inactivity
Low high density lipoprotein (HDL)
Familial Hypercholesterolemia (FH)
• Mutation of the LDL
receptor leads to defective
uptake and degradation of
the LDL
• Autosomal dominant
pattern
Familial Hypercholesterolemia
Presentation
Tendon Xanthomas
--Premature coronary artery disease that can
present during childhood.
--Myocardial infarction as early as 40 years of age
--Tendon xanthomas
--Xanthelesmata
--Premature arcus cornealis
Arcus Cornealis
Xanthalesmata
Familial Hypercholesterolemia
Labs
• Heterozygous mutation:
• LDL >220 mg/dL (desirable <100)
• Homozygous mutation
• LDL >550 mg/dL
Treatment
• Low fat diet and daily exercise
• HMG CoA reductatse inhibitors
(Statins)
• Nicotinic Acid
• Bile Acid sequestrants
Lipoprotein Lipase Deficiency (LPL)
• Deficiency in LPL or its
cofactor Apo C-II impairs
uptake of triglycerides into
the peripheral tissues
• Autosomal recessive
LPL Deficiency Presentation
--Diagnosed always in
childhood
--Eruptive xanthomas
--Lipemia retinalis
--Pancreatitis
--Hepatospleenomegaly
--Triglycerides >1500
mg/dL (desirable <150)
Eruptive xanthomas
Lipemia Retinalis
LPL deficiency
Fasting Labs
• Triglycerides >1500
Treatment
• Omega -3 fatty acid
• Lovaza (Omega-3-Acid Ethyl Esters)
3-4 grams daily
• Over the counter fish oil 1-4 grams
daily
Familial Hypertriglyceridemia
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Caused by overproduction of triglycerides
Genetic defect has not been established
Autosomal dominant
Diagnosed in adulthood
Xanthomas
Pancreatitis
Familial Hypertriglyceridemia
Labs
• Fasting triglycerides >150-500
mg/dl or greater if person is obese,
consumes alcohol or has diabetes
Treatment
• Fibric acids
• Gemfibrozil (Lopid) 600 mg
twice daily
• Fenofibrate (Tricor) 135-200
mg daily
• Nonalcoholic fatty liver disease and
nonalcoholic steatohepatitis (NASH)
• Fatty liver disease in the absence of
alcohol ingestion
• Characterized by inflammation of the liver
with concurrent fat accumulation resulting
in liver cirrhosis
• The pathophysiology is not well
understood but there is elevated
triglycerides and liver enzymes
• Risk factors for NASH
• Diabetes
• Obesity
• Metabolic Syndrome
Nonalcoholic fatty liver disease and
nonalcoholic steatohepatitis (NASH)
Laboratory Findings:
--Elevated triglycerides >200 mg/dL (<175)
--Elevated alanine aminotransferase (ALT) >40 U/L (10-40)
--Elevated aspartate aminotransferase (AST) >56 U/L (7-56)
Imaging: liver ultrasound or CT scan
Liver biopsy: definite diagnosis
Treatment : Weight loss, healthy diet, avoid alcohol
Metformin (Glucophage) 500 mg twice daily or
Pioglitazone (Actos) 15 mg daily (max 45 mg daily)
Vitamin E 1000 mg/daily